e24046 Background: Secondary lymphedema and fibrosis occurs in more than 90% of HNC survivors. Given the progressive nature of lymphedema, prompt identification and treatment are essential. Treatment of HNC related lymphedema is fraught by numerous barriers. Advanced pneumatic compression devices (APCD) may address critical barriers. We conducted a phase 3 randomized multi-site trial in HNC survivors with treatment naïve lymphedema comparing usual care to APCD. Here in we report a qualitative analysis of participants treatment experience. Methods: Semi-structured interviews were audio recorded and transcribed after participants completed the 6 th -month visit (N = 14 usual care, N = 23 APCD). Questions addressed treatment experience, perceptions of care, barriers, and facilitators. A hierarchical coding system was developed and refined using the interview guide and preliminary review of the transcripts. Transcripts were coded by experienced qualitative researchers. The coded transcripts were analyzed using an iterative inductive-deductive approach and based on our theoretical framework. Results: Participants were 65% male, 35% female and identified as 92% white, 5% black, and 5% Hispanic. The average age was 62 with a range of 32-82. We identified two distinct and one common set of barriers and facilitators. For usual care, health system (care coordination, logistics) and therapist factors (perceived skills and demeanor) were important while device characteristics (fit, comfort) were important for the APCD. Cognitive affective factors (self-efficacy, knowledge, outcome expectations, frustration) were similar for both therapies and interacted with the device/system characteristics. Conclusions: We identified distinct treatment barriers and facilitators for usual lymphedema care and treatment with APCD. Barriers identified in this study highlight practice changing opportunities to address system issues and develop interventions to enhance care and quality of life. Utilization of both treatment strategies may allow tailoring of treatments thus optimizing outcomes. Clinical trial information: NCT04797390 .
12123 Background: Pain is ubiquitous in head and neck cancer (HNC) patients undergoing radiotherapy (RT) with up to 40% developing chronic pain. Gabapentin initiated concurrently with RT reduces pain intensity, opioid use, and dysphagia; however, gabapentin may not fully control pain, and dose escalation may be limited by toxicity. Novel non-opioid analgesic combinations administered concurrent with RT may address these limitations. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor modulates mood and pain and is involved in central sensitization. Blocking the NMDA receptor may decrease the development and severity of neuropathic pain and decrease/prevent central sensitization. In combination with other analgesics, ketamine may enhance acute and chronic pain control at lower doses thus avoiding dose-limited toxicities. We report results from the dose-finding phase I study of gabapentin plus intranasal (NAS) ketamine in HNC patients undergoing RT; phase II is ongoing. Methods: Eligibility: locally advanced non-metastatic HNC planned for primary or adjuvant RT with or without concurrent chemotherapy. Primary objective of phase I was to determine the maximum tolerated dose (MTD) or maximum planned dose (MPD) for NAS ketamine combined with gabapentin (300mg TID). Planned dose levels (DL) were DL1: 10 mg TID, DL2: 20 mg TID, DL3: 30 mg TID and DL 4: 40 mg TID. A phase II expansion was planned at the MTD/MPD to confirm safety and feasibility. Results: Eleven patients were enrolled during phase I, which has been completed. No dose limiting toxicities (DLTs) were noted at DL1, DL2 or DL3. Two DLTs were reported at DL4: grade 2 dizziness and grade 2 sedation. The MTD was ketamine 30 mg NAS TID. Six patients are enrolled on the phase II trial at the MTD which is ongoing. Conclusions: The MTD of NAS ketamine was 30mg TID combined with gabapentin 300mg. The Phase II expansion is ongoing. Clinical trial information: NCT05156060 .
This study was an examination of dental care utilization among survivors of early life cancers (cancer diagnosis at 20 years of age or younger) and the extent to which socio-economic factors may present a barrier to care. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 (n = 28,640). Survey-weighted regression models were used to evaluate associations between early life cancers and subsequent frequency of dental care as adults. A mediation analysis was conducted to test education and household income as potential mediators of this association using a non-parametric bootstrap approach. Early life cancers were associated with a significant decrease in dental care utilization as adults (OR:0.459, 95%CI:(0.226, 0.935)). This diminished utilization was particularly pronounced with survivors in their 20s and 30s. Over time dental care utilization began a slow recovery. The association between early cancer and level of education was estimated to be negative but did not reach statistical significance (OR:0.739, 95%CI:(0.503, 1.086),
Mutations in alkaline phosphatase (AlkP), liver/bone/kidney (ALPL), which encodes tissue-nonspecific isozyme AlkP, cause hypophosphatasia (HPP). HPP is suspected by a low-serum AlkP. We hypothesized that some patients with bone or dental disease have undiagnosed HPP, caused by ALPL variants. Our objective was to discover the prevalence of these gene variants in the Vanderbilt University DNA Biobank (BioVU) and to assess phenotypic associations. We identified subjects in BioVU, a repository of DNA, that had at least one of three known, rare HPP disease-causing variants in ALPL: rs199669988, rs121918007, and/or rs121918002. To evaluate for phenotypic associations, we conducted a sequential phenome-wide association study of ALPL variants and then performed a de-identified manual record review to refine the phenotype. Out of 25,822 genotyped individuals, we identified 52 women and 53 men with HPP disease-causing variants in ALPL, 7/1000. None had a clinical diagnosis of HPP. For patients with ALPL variants, the average serum AlkP levels were in the lower range of normal or lower. Forty percent of men and 62% of women had documented bone and/or dental disease, compatible with the diagnosis of HPP. Forty percent of the female patients had ovarian pathology or other gynecological abnormalities compared with 15% seen in controls. Variants in the ALPL gene cause bone and dental disease in patients with and without the standard biomarker, low plasma AlkP. ALPL gene variants are more prevalent than currently reported and underdiagnosed. Gynecologic disease appears to be associated with HPP-causing variants in ALPL.
Background Acute kidney injury ( AKI ) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI . High‐density lipoproteins ( HDLs ) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL 's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association. Methods and Results We tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI . A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change ( P =0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients ( P =0.008) and was further enhanced with perioperative atorvastatin treatment ( P =0.004) and increasing long‐term statin dose ( P =0.003). Conclusions A higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique Identifier: NCT 00791648.
Acute kidney injury (AKI) after cardiac surgery occurs in up to 30% of patients and predicts death. We have reported that a higher preoperative HDL particle concentration is independently associated with a decreased risk of AKI after cardiac surgery. HDL has known anti-oxidant properties that may attenuate AKI. We hypothesized that HDL particle size is associated with paraoxonase-1 (PON-1) activity and with the risk of AKI after cardiac surgery. We selected 90 patients who developed mild, moderate, severe, or no AKI from a prospective trial of perioperative atorvastatin to prevent post-cardiac surgery AKI. PON-1 paraoxonase activity was measured in apoB-depleted serum with fluorescent substrate 7-diethylphospho-6,8-dixuor-4-methylumbelliferyl. HDL particle size was assessed using the NMR Lipoprofile test. Linear regression was used to assess the association between preoperative small, medium, and large HDL particle concentrations and PON-1 activity. We assessed the association between HDL particle levels and the maximum serum creatinine change from baseline in the first 48 postoperative hours using two-component latent variable mixture models adjusted for AKI risk factors. A higher preoperative small HDL particle concentration was associated with a higher preoperative PON-1 activity (p=0.003, Figure 1A). Medium and large HDL particle concentrations were not associated with PON-1 activity. Small HDL particle concentration was found to be independently associated with postoperative serum creatinine change (p=0.02, Figure 1B), while medium and large HDL particle concentrations were not. Conclusions: A higher preoperative small HDL particle concentration was associated with a higher PON-1 activity and a decreased risk of AKI after cardiac surgery. Future work will characterize HDL throughout the surgical course to identify the mechanism underlying the protective association between HDL and AKI.
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